title: Medicinal chemistry inspired fragment-based drug discovery.
abstract: Lead generation can be a very challenging phase of the drug discovery process. The two principal methods for this stage of research are blind screening and rational design. Among the rational or semirational design approaches, fragment-based drug discovery (FBDD) has emerged as a useful tool for the generation of lead structures. It is particularly powerful as a complement to high-throughput screening approaches when the latter failed to yield viable hits for further development. Engagement of medicinal chemists early in the process can accelerate the progression of FBDD efforts by incorporating drug-friendly properties in the earliest stages of the design process. Medium-chain acyl-CoA synthetase 2b and ketohexokinase are chosen as examples to illustrate the importance of close collaboration of medicinal chemists, crystallography, and modeling.
authors.affiliation: Medicinal Chemistry, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Spring House, Pennsylvania, USA.
authors.forename: James
authors.initials: J
authors.lastname: Lanter
authors.forename: Xuqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Sui
mesh_terms: D002626:Chemistry, Pharmaceutical; D003066:Coenzyme A Ligases / Q000378:metabolism; D018360:Crystallography, X-Ray; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005631:Fructokinases / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship
chemical_list: D054852:Small Molecule Libraries; D005631:Fructokinases; C021475:ketohexokinase; D003066:Coenzyme A Ligases